Association between C-reactive protein levels and outcome in acute lung injury in children.

UNLABELLED: High plasma C-reactive protein (CRP) levels are associated with favorable outcome in adults with acute lung injury (ALI). The association between CRP levels and outcome has not been studied in ALI in children. We performed a historical cohort study in 93 mechanically ventilated children (0-18 years) with ALI. The CRP level within 48 h of disease onset was tested for association with 28-day mortality and ventilator-free days (VFD). Clinical parameters and ventilator settings were evaluated for possible confounding. Fourteen patients died within 28 days. The median (interquartile range) CRP level in nonsurvivors was 126 mg/L (64; 187) compared with 56 mg/L (20; 105) in survivors (p = 0.01). For every 10-mg/L rise in CRP level, the unadjusted odds (95% confidence interval (95% CI)) for mortality increased 8.7% (2.1-15.8%). Cardiovascular organ failure at onset of ALI was the strongest predictor for mortality (odds ratio, 30.5 (6.2-152.5)). After adjustment for cardiovascular organ failure, for every 10-mg/L rise in CRP level, the OR (95% CI) for mortality increased 4.7% (-2.7-12.6%; p = 0.22). Increased CRP levels were associated with a decrease in VFD (ρ = -0.26, p = 0.01). CONCLUSION: increased plasma CRP levels are not associated with favorable outcome in ALI in children. This is in contrast with findings in adults with ALI.

The impact of changing toward higher welfare broiler production systems on greenhouse gas emissions: a Dutch case study using life cycle assessment.

In the Netherlands, the Dutch Retail Broiler (DRB) and Better Life one Star (BLS) production systems have been introduced with the aim to improve broiler welfare. Simultaneously, retailers set targets for reduction of greenhouse gas (GHG) emissions in the whole broiler production chain. The GHG emissions of DRB and BLS may differ from conventional systems because of differences in slaughter age, feed intake, and diet composition. The aim of this study was to estimate GHG emissions of the conventional, DRB, and BLS production systems. A deterministic, spreadsheet based model was developed that included the breeder, hatchery, and broiler farm stages. First, the model calculates feed intake of different diets and energy use, based on performance objectives and literature. Selection of feed ingredients for the different types of diets was based on least cost formulation with nutritional constraints for each diet. Second, GHG emissions were estimated from cradle to broiler farm gate for processes along the broiler production chain by using life cycle assessment, and expressed as kg CO2-equivalents per kg live weight (kg CO2-eq/kg LW). Results showed that BLS (3.55 kg CO2-eq/kg LW) had lower GHG emissions compared to conventional (3.65 kg CO2-eq/kg LW) and DRB (3.98 kg CO2-eq/kg LW) at the broiler farm gate. Emissions from land use change (LUC) from feed production, mainly from soybean products, had highest impact on total GHG emissions (>50%) for the systems and these soybean products had the lowest inclusion in the diets of the BLS production system. Sensitivity analyses showed that variation in slaughter weight and feed intake could result in overlap of GHG emissions between systems. When soybean products were sourced from a country with low LUC emissions, conventional (1.37 kg CO2-eq/ kg LW) had the lowest GHG emissions and BLS (1.79 kg CO2-eq/kg LW) the highest. This study showed that origin of and including or excluding LUC emissions from soybean production results in different conclusions for achieving the GHG emissions reduction targets set by retailers.

Food safety in free-range and organic livestock systems: risk management and responsibility.

Animal production systems that offer outdoor access to the animals have become increasingly popular in the Western world due to the growing general discontent of consumers with conventional bioindustrial farming practices. These open production systems offer improved animal welfare but may create new problems for animal health, resulting in increased food safety risks from bacterial, viral, or parasitic infections or environmental contaminants. Examples of these new problems include increased Toxoplasma gondii infections in pigs and high dioxin levels in eggs from free-range hens. In this review, the relation between positive and negative points of free-range and organic livestock production systems is discussed with reference to production in The Netherlands. We investigated how proponents of more animal welfare friendly systems deal with potential negative issues in public and whether any risk communication is used. Generally, we found that the existence of a dilemma is disputed or avoided in communication with the consumer. This avoidance could be detrimental for public trust in alternative animal production systems, should problems occur. To prevent future problems, it will be necessary to communicate about the relevant types and sources of the food safety risks to the consumers. The responsibility for protecting food safety should be properly divided among the various parties involved: producers, processors, governments, nongovernmental organizations, and consumers.

ACE mediates ventilator-induced lung injury in rats via angiotensin II but not bradykinin.

Ventilator-induced lung injury is characterised by inflammation and apoptosis, but the underlying mechanisms are poorly understood. The present study proposed a role for angiotensin-converting enzyme (ACE) via angiotensin II (Ang II) and/or bradykinin in acute lung injury. The authors assessed whether ACE and, if so, Ang II and/or bradykinin are implicated in inflammation and apoptosis by mechanical ventilation. Rats were ventilated for 4 h with low- or high-pressure amplitudes in the absence or presence of the ACE inhibitor captopril. Nonventilated animals served as controls. ACE activity, Ang II and bradykinin levels, as well as inflammatory parameters (total protein, macrophage inflammatory protein-2 and interleukin-6) were determined. Apoptosis was assessed by the number of activated caspase-3 and TUNEL (terminal deoxynucleotidyltransferase-mediated deoxyuridine triphosphate nick-end labelling)-positive cells. Bronchoalveolar lavage fluid ACE activity, levels of total protein, inflammatory parameters and the number of apoptotic cells were increased in the high-pressure amplitude group as compared with the control group. Blocking ACE activity by captopril attenuated inflammation and apoptosis in the latter group. Similar results were obtained by blocking Ang II receptors, but blocking bradykinin receptors did not attenuate the anti-inflammatory and anti-apoptotic effects of captopril. The current authors conclude that inflammation and apoptosis in ventilator-induced lung injury is, at least in part, due to angiotensin-converting enzyme-mediated angiotensin II production.

Modelling the effect of sub(lethal) heat treatment of Bacillus subtilis spores on germination rate and outgrowth to exponentially growing vegetative cells.

Spores of Bacillus subtilis were subjected to relatively mild heat treatments in distilled water and properties of these spores were studied. These spores had lost all or part of their dipicolinic acid (DPA) depending on the severity of the heat treatment. Even after relatively mild heat treatments these spore lost already a small but significant amount of DPA. When these spores were inoculated in nutrient medium-tryptone soy broth (TSA)-the non-lethally heated spores started to germinate. Results of classical optical density measurements showed that both phase darkening and subsequent outgrowth could be affected by sub-lethal heat. A study of single cells in TSB showed that lag times originating from exponentially growing cells followed a normal distribution, whereas lag times originating from spores followed a Weibull distribution. Besides classical optical density measurements were made to study the effect of previous heating on the kinetics of the first stages of germination. The germination kinetics could be described by the model as was proposed by Geeraerd et al. [Geeraerd, A.H., Herremans, C.H. and Van Impe, J.F., 2000. Structural model requirements to describe microbial inactivation during a mild heat treatment. International Journal of Food Microbiology 59, 185-209]. Two of the 4 parameters of the sigmoid model of Geeraerd were dependent on heating time and heating temperature, whereas the two other parameters were considered as independent of the heating conditions. Based on these observations, a secondary model could be developed that describes the combined effect of heating temperature and heating time on the kinetics of germination. To have more detailed information of the kinetics of germination samples incubated in TSB were tested at regular time intervals by flow cytometry. To that end the cells were stained with syto 9 to distinguish between the various germination stages. There was a qualitative agreement between the results of flow cytometry and those of optical density measurements, but there was a difference in quantitative terms. The results have shown that germination rate of spores is dependent on previous heating conditions both in the first stage when phase darkening occurs and also during the later stages of outgrowth when the phase dark spore develops to the vegetative cell.

High incidence of acute lung injury in children with Down syndrome.

OBJECTIVE: Acute respiratory tract infection is a common reason for hospitalization in children with Down syndrome (CDS) and is characterized by a high morbidity. The severe course of disease in CDS may be related to a higher incidence of acute lung injury (ALI). This study evaluated the incidence of ALI and acute respiratory distress syndrome (ARDS) in mechanically ventilated CDS. DESIGN AND SETTING: Retrospective cohort study in a pediatric ICU. PATIENTS AND PARTICIPANTS: Cases were all mechanically ventilated CDS admitted to our unit between January 1998 and July 2005. All mechanically ventilated patients without Down syndrome from January 1998 to January 2001 served as controls. Postoperative patients (cases and controls) and those with a cardiac left to right shunt were excluded. MEASUREMENTS AND RESULTS: The main outcome measure was the incidence of ALI and ARDS. The criteria for ALI were met in 14 of 24 CDS (58.3%) in 41 of 317 of controls (12.9%; OR 9.4, 95% CI 3.9-22.6). The criteria for ARDS were met in 11 of 24 CDS (46%) and in 21 of 317 of controls (7%; OR 11.9, 95% CI 4.8-29.8). None of the CDS with ALI died; in the control group ten patients with ALI died. CONCLUSIONS: CDS had a significantly higher incidence of ALI and ARDS than children without Down syndrome. The explanation for this remains to be elucidated; further study is necessary before clinical implications become clear.

Absence of human metapneumovirus co-infection in cases of severe respiratory syncytial virus infection.

It has been suggested that co-infection of human metapneumovirus (hMPV) in severe respiratory syncytial (RSV) virus bronchiolitis is very common. To evaluate the epidemiology of hMPV co-infection in children with severe lower respiratory tract infection caused by RSV virus. This was an observational cohort study in which hMPV and RSV viral load was measured by RT-PCR in tracheal specimens from the target population. hMPV could not be detected in any of the 30 mechanically ventilated children with RSV lower respiratory tract infection. Our study suggests that hMPV co-infection is not very common in severe RSV lower respiratory tract infection.

[The practice guideline 'Volume suppletion in critically-ill neonates and children up to the age of 18 years' of the Dutch Paediatric Association]. / Richtlijn 'Volumesuppletie bij kritisch zieke pasgeborenen en kinderen tot 18 jaar' van de Nederlandse Vereniging voor Kindergeneeskunde.

Hypovolaemia is the most common cause of circulatory failure in children. Treatment consists of volume suppletion with a crystalloid or colloid solution; which agent is the best in children is not clear. This evidence-based practice guideline formulates recommendations as to which fluid should be used for volume suppletion in critically-ill neonates and children up to the age of 18 years with hypovolaemia. Before the guideline development first-choice fluid for volume resuscitation was in 50% a colloid and in 50% a crystalloid solution for both neonatologists and paediatric intensivists. The neonatologists used human albumin as a priority, and the paeditric intensivists predominantly used a synthetic colloid. The guideline was developed on the basis of a comprehensive search and analysis of the literature according to the principles of evidence-based guideline development. The recommendations were formulated by a committee based on evidence from the literature and, when evidence from the literature was insufficient, on consensus after discussion in the committee. Since colloids are much more expensive than crystalloids and can give an anaphylactic reaction, their added value over crystalloids must be proven. In sick neonates and children, insufficient clinical trials have been done to reach the conclusion that colloids are more effective than crystalloids in hypovolaemia. A number of meta-analyses in adults revealed excess mortality in the group treated with albumin, but one recent, large, randomised study showed no difference in mortality. No added value could be demonstrated for the administration of synthetic colloids. On the basis of data from the literature and considerations regarding the applicability of evidence in adults to children and neonates, the side effects of resuscitation fluids, pathophysiology and costs, the first-choice fluid for neonates and children with hypovolaemia is isotonic saline. Albumin should not be used for the treatment of hypovolaemia. The volume to be administered and the infusion rate depend on the severity of the hypovolaemia and should be determined on an individual basis.

[Late presentation of congenital diaphragmatic hernia]. / Late presentatie van aangeboren hernia diaphragmatica.

A boy aged 6 months and a girl aged 9 months were admitted due to vomiting, among others, and a boy aged 11 months due to pneumonia. It turned out that they had a congenital diaphragmatic hernia. Primary operative repair was performed successfully in all patients, followed by recovery. The older boy experienced a relapse nearly 1 year later, which was treated by surgical correction. Most congenital diaphragmatic hernias present directly after birth, with cyanosis and respiratory distress. However, 10-20% of the cases are discovered after this period. In these children diagnosis can be difficult because of the diverse symptoms such as vomiting, feeding difficulties, tachypnoea or recurrent respiratory tract infections. Physical signs include the absence of breath sounds or the presence of bowel sounds in the chest. Chest X-ray, contrast upper gastrointestinal series or ultrasound imaging confirms the diagnosis. Delay in treatment can lead to complications such as necrosis of the bowel. In young children with acute or chronic respiratory infections or gastrointestinal complaints, a congenital diaphragmatic defect should be considered.

Cerebro-costo-mandibular syndrome.

We describe two boys with the cerebro-costo-mandibular syndrome (CCMS). Both patients presented with Pierre Robin anomaly and respiratory insufficiency and died 12 hours and 10 months after birth. The first boy had muscular hypotonia, severe micrognathia, glossoptosis, short palate, preauricular tag, paraumbilical fibroma, and a small and narrow thorax. His chest roentgenographs showed marked hypoplasia of the first to tenth rib, multiple posterior rib-gaps in the only four ossified ribs. Tracheomalacia and stenosis of the left ureter was observed during autopsy. No structural cerebral anomalies were observed. Respiratory distress necessitated a tracheostomy in the second boy. He had severe micrognathia with glossoptosis and a cleft soft palate were noted. His chest roentgenograph showed a bell-shaped, small thorax with multiple dorsal rib-gap defects. CCMS is a rare disorder often associated with Pierre Robin anomaly. Chest roentgenographs show the typical posterior rib-gap defects, which are quite variable. CCMS usually occurs as an isolated event in a family. Of 41 reported families four reports describe horizontal and two describe vertical transmission of CCMS. This might imply genetic heterogeneity with autosomal recessive and autosomal dominant inheritance. Inter- and intrafamilial expression is variable. Careful family studies are necessary before genetic counseling is given.

Cardiopulmonary resuscitation in paediatric intensive care patients.

To identify the success of cardiopulmonary resuscitation in the paediatric ICU patient we undertook a retrospective study in an 11-bed medical and a 14-bed surgical paediatric ICU over a 32-month period. Thirty-four patients suffered an arrest in the ICU. Only 4 patients could be resuscitated successfully; 1 died after 24 h. Of the 3 long-term survivors 1 suffered from severe neurologic sequelae. All patients were in CCS classes III or IV. All but 3 patients had PSI scores greater than 8. The decision to resuscitate or to withhold therapy in individual patients who are deteriorating in the course of a critical, preceding illness should not be based on the risk index of these scoring systems. Both medical and ethical considerations should be guidelines in the process of decision-making.

Experiences with Guillain-Barré syndrome in a pediatric intensive care unit.

During a 10-year period 16 children with acute Guillain-Barré syndrome were seen. Eleven were admitted to the Pediatric Intensive Care Unit, either because of difficulty of breathing and swallowing or because of symptoms of autonomic disturbance. Six patients were mechanically ventilated for a mean period of 17 days. Symptoms of autonomic disturbance were frequently seen especially in the mechanically ventilated patients. Two patients died because of cardiac arrhythmia. Methods of detecting patients at risk for cardiac dysrhythmia are suggested.

Radiographic evidence of bronchopulmonary dysplasia in high-risk congenital diaphragmatic hernia survivors.

Congenital diaphragmatic hernia is a congenital malformation associated with pulmonary hypoplasia. It often leads to respiratory failure, requiring artificial ventilation with high inflation pressures and high percentages of oxygen. We evaluated radiographic evidence of bronchopulmonary dysplasia (BPD) in survivors, who presented with respiratory distress within 6 hours after birth, by a radiographic scoring system measuring the severity of BPD by the Toce score and the degree of pulmonary hypoplasia by the Touloukian score. Fifteen of 45 survivors (33 percent) had clinical and radiological lung disease resembling BPD. As a group they had significantly higher Touloukian and Toce scores than survivors without BPD. Morbidity expressed as the duration of artificial ventilation, supplemental oxygen, and hospital stay was much higher in the BPD group. The hypoplastic lung in infants with congenital diaphragmatic hernia appears to be as susceptible to barotrauma and pulmonary oxygen toxicity as the lungs of prematurely born infants. To what extent BPD occurring in congenital diaphragmatic hernia survivors might influence the future development of lung function is not yet known.

Postoperative care after craniofacial surgery: evaluation of routine laboratory testing.

In this study, two protocols for monitoring children after major craniofacial surgery were compared. The first protocol consisted of repetitive laboratory testing in 37 children to detect surgical and medical complications during a 2-year period. None of the complications were predicted by abnormal test results, and abnormal results of routinely performed tests never led to a change in management. The second protocol, an adapted version of the first protocol, was continued for 5 years as a prospective study in 98 children: Patients were routinely tested only once, and further testing was initiated either after an abnormal test result or because of clinical symptoms. Clinical management and the incidence of postoperative complications did not differ between groups. The second protocol considerably reduced the mean number of tests per patient from 42.5 to 7.0, but in contrast with the first protocol, 84 percent of abnormal test results led to changes in clinical management. In conclusion, in the first group the test results were not used and were not predictive of complications. In the second group, tests were more apt to have abnormal results and often initiated treatment. This shows that indiscriminate routine laboratory testing is of limited value in covering the postoperative period after craniofacial surgery.

Persistent pulmonary hypertension in high-risk congenital diaphragmatic hernia patients: incidence and vasodilator therapy.

Survival of congenital diaphragmatic hernia patients depends on the gravity of pulmonary hypoplasia and persistent pulmonary hypertension (PPH). Many vasoactive drugs have been used in the treatment of PPH, but often they also lower peripheral resistance, leading to a significant drop in arterial blood pressure. The incidence of PPH in 52 high-risk diaphragmatic hernia patients and the results of treatment with tolazoline and prostacyclin were evaluated in a study lasting 52 months and involving 52 patients. High-risk patients require ventilatory support within 6 hours after birth. Study parameters were alveolar-arterial oxygenation difference (AaDO2), oxygenation index (OI), and mean arterial blood pressure (MABP), measured at set times before and after administration of tolazoline or prostacyclin. Twenty-one patients had documented episodes of PPH (46%), and 18 of them died. Tolazoline did not lower AaDO2 and OI values, but MABP dropped significantly. Prostacyclin caused a significant decrease of AaDO2 and OI values without an effect on MABP. We concluded: (1) PPH presented in 46% of our patients, associated with a high mortality rate; (2) tolazoline is not an effective dilator of the pulmonary vascular bed and lowers MABP; and (3) prostacyclin is an effective pulmonary vasodilator as reflected by ventilation parameters without systemic side effects; it does not affect overall outcome but can used as a "bridge" to extracorporeal membrane oxygenation.

Withholding and withdrawal of life support from surgical neonates with life-threatening congenital anomalies.

We evaluated why and how life support was withheld or withdrawn in surgical neonates. During the study period, January 1988 through December 1991, 529 neonates were admitted, 52 of whom died (10%). Twenty-eight deaths were due to the underlying disease. The other 24 patients died because treatment was withheld or withdrawn. In 15 of 24 (group A, mean stay 9.2 +/- 9.1 days) treatment was initially started but later withdrawn (13/15) because of the severity of congenital anomalies alone (7/12) or congenital anomalies associated with chromosomal anomalies (5/12). In 9 of 24 (group B, mean stay 20.3 +/- 17.3 days) treatment was withdrawn because of serious complications. In all cases often lengthy discussions have led the doctors and nurses together with the parents to chose unanimously for withdrawal of treatment. Mechanical ventilation was the intervention most frequently withdrawn (10/15 group A, 9/9 group B). Vasoactive and other drugs were withheld in 5 patients of group A. Sedatives and analgetics were administrated as supportive care permitting the child to die in a humane way, 17 in the lap of a parent and 7 in the lap of a nurse. We conclude that life-sustaining care is withheld or withdrawn relatively frequently from patients at our ICU. Such decisions are ethical ones, taken in the light of professional and technical expertise. Evaluation of withholding or withdrawal of treatment is difficult but necessary to evolve appropriate decision-making procedures and to formulate humane standards of intensive care.(ABSTRACT TRUNCATED AT 250 WORDS)

Carnitine deficiency in surgical neonates receiving total parenteral nutrition.

Carnitine plays a key role in the oxidation of fatty acids. Most solutions for parenteral nutrition do not contain carnitine. Because endogenous carnitine synthesis is insufficient in newborns, they are prone to developing a carnitine deficiency when they are dependent on total parenteral nutrition (TPN). Stimulated by the clinical observation of manifest clinical symptoms of carnitine deficiency in one patient, a study of 13 consecutive neonates who received TPN for over 2 weeks was begun. Their plasma carnitine levels before and during carnitine supplementation were determined. All patients had a carnitine intake far below the recommended minimal need of 11 mumol/kg per day. Although only three of them clearly showed clinical symptoms described as carnitine deficiency, carnitine supplementation for all neonates receiving TPN for over 2 weeks is recommended.

Incidence and management of gastroesophageal reflux after repair of congenital diaphragmatic hernia.

During a period of 6 years, 31 of 54 infants with congenital diaphragmatic hernia survived and were evaluated to study incidence and management of gastroesophageal reflux. At 6 months' follow-up 16 patients had gastroesophageal reflux proven by upper gastrointestinal series; at 12 months' follow-up 11 patients. Three patients having gastroesophageal reflux did not respond to medical treatment and underwent Nissen fundoplication. We conclude that after successful treatment, congenital diaphragmatic hernia is likely to be complicated by gastroesophageal reflux. We could not define a predictive feature for gastroesophageal reflux in the individual patient surviving congenital diaphragmatic hernia.

Congenital diaphragmatic hernia: impact of preoperative stabilization. A prospective pilot study in 13 patients.

In case of congenital diaphragmatic hernia (CDH), survival generally depends not on prenatal diagnosis, planned delivery, and immediate postnatal operation, but on the gravity of pulmonary hypoplasia and persistent hypertension (PPH). Many vasoactive drugs have become available for lowering PPH, but the mortality rate for CDH still amounts to 40% to 70%. Preoperative stabilization might prevent or at least reduce the risk of PPH. This method was evaluated in a pilot study lasting 15 months and involving 13 patients. All were admitted to the pediatric surgical intensive care unit within six hours of birth, all requiring mechanical ventilation. Continuous suction of the stomach and bowel proved successful in reducing the mediastinal shift. Study parameters were alveolar-arterial oxygenation differences ((A-a)DO2), mean airway pressure (MAP), oxygenation index (OI), and ventilation index (VI), measured on admission and at set times before and after surgery. Eight patients did not survive, but in two cases death was not directly related to CDH. The following conclusions were reached: (1) satisfactory ventilation parameters on admission will remain good during the preoperative stabilization phase and will not be affected by its duration or by subsequent surgery, spelling survival; (2) unsatisfactory ventilation parameters on admission may improve with preoperative stabilization, giving these patients a better chance of survival; and (3) poor ventilation parameters on admission that fail to improve with preoperative stabilization will not improve with surgery or postoperatively, spelling death.